Sentinel Lymph Node Mapping in Breast Cancer

Sentinel Lymph Node Mapping in Breast Cancer

Sentinel node surgery for breast cancer has generated considerable
interest, and the timely article by Dr. Cody provides a concise,
well-written review of the topic. This commentary will add a few
relatively minor points and will offer some alternative viewpoints to
the authors conclusions.

Historical Perspective

It is interesting that Ramon Cabanas verbalized the modern concept of
the sentinel nodes at the Society of Surgical Oncology hosted by
Memorial Sloan-Kettering Cancer Center (Dr. Codys institution)
22 years ago. Dr. Cabanas reported that, in penile cancer, sentinel
nodes were the first nodes to receive cancer cells from a primary
tumor and, importantly, that the status of these nodes (obtained
through a minor surgical biopsy) would allow a decision to be made as
to whether a complete lymphadenectomy should be performed.[1]
Although Cabanas appears to be the first person to declare the
utility of sentinel node surgery, many others throughout this century
have documented and understood the concept of primary or sentinel nodes.

As early as 1915, Dr. Braithwaite of England recognized that
glands sentinel were the initial nodal drainage basins
from specific locations within the abdominal cavity.[2] Since
Braithwaites fundamental observations, drainage to a limited
set of nodes has been demonstrated for tumors of the stomach
(targeting the primary nodes[3]), lung (mapping of
the nodes by vital staining[4]), testicles (primary
complex of nodes[5,6] and the metastatic emboli from a
primary testicular tumor could find their first filter in this lymph
center[7]), breast,[8] and upper gastrointestinal tract.[9]

A wide variety of tracers have been used to identify sentinel nodes.
Colored dyes that vividly delineate the lymphatic channels leading to
sentinel nodes and also usually stain the nodes have been used
throughout this century. Since the 1930s, radiopaque contrast has
also been used,[10] and has been injected interstitially (indirect
lymphography) or directly into the lymphatic channels (direct lymphography).

After World War II, radioactive tracers became more readily available
and were used to label lymph nodes draining cancers of the
cervix,[11] breast,[12] lung,[13] head and neck ,[14] rectum,[15] and
prostate.[16] Gamma camera imaging of lymph ducts and nodes
(lymphoscintigraphy) was used extensively following its introduction
in 1958.[17] Handheld gamma detectors have been used intraoperatively
to locate radiolabeled tissues for decades[18,19] but were introduced
in 1993 for the identification of sentinel nodes.[20-22]

Radiolabeling of sentinel nodes can be performed successfully with a
variety of radioactive tracers. It is very encouraging that within a
few short years, an otherwise challenging technique has emerged as a
routinely successful procedure with a high level of accuracy.

A Recent Study

The review by Dr. Cody covers the majority of reports available.
Since the paper was written, a multicenter study has been reported
confirming that sentinel node surgery can be successful in a variety
of clinical settings after a short period of mentored training.[23]
This study also demonstrated that drainage to sentinel nodes outside
of the axilla occurred in almost 1 out of 10 patients. This was
clinically meaningful in that 3% of all node-positive cases occurred
exclusively in nodes outside of the axilla.

Although recent modifications appear to minimize false-negative
cases,[24] the rate of false-negativity will probably not reach 0%.
It can be expected that, in a small percentage of patients who have
pathologically negative sentinel nodes, there will be nodes left
behind that contain cancer cells. This very important issue will be
addressed in the National Surgical Adjuvant Breast and Bowel Project
sentinel node clinical trial (NSABP-32).

Total Lymphadenectomy vs Sentinel Node Resection

There are three rationales for performing node resection in patients
with breast cancer: (1) staging, (2) regional control, and (3) the
possibility of improved survival. Axillary lymphadenectomy addresses
all three goals. Sentinel node surgery accomplishes staging with
relatively high accuracy (at least with regard to whether or not
nodal metastases have occurred). However, to date there are no data
on the impact of sentinel node surgery alone (without axillary
lymphadenectomy) on locoregional control or survival.

The B-32 sentinel node trial is analogous to the NSABP-06 trial,
which compared total mastectomy to partial mastectomy. The B-32 trial
will compare total lymphadenectomy to partial lymphadenectomy
(sentinel node resection). The end points of the B-32 trial are
similar to those of the B-06 trial and include long-term regional
(local) control and survival. Although these end points should be
similar in both randomized arms, morbidity should be markedly reduced
in the sentinel node resection arm.

Is Sentinel Node Surgery Ready for Prime Time?

A crucial question is whether sentinel node surgery is ready for
prime time. The answer is, yes and no: yes, in that the
accuracy of sentinel node resection appears to be high enough for
staging purposes; and no, in that there are no data as yet comparing
the ability of sentinel node surgery to provide long-term regional
control. Furthermore, if we later found out that decreased morbidity
were achieved at the price of decreased survival (even if that
decrease were very small), how would the procedure be viewed? No
single surgeon or institution can answer these critical questions.

Patients and physicians have had to contend with so much uncontrolled
data for so long that it is hardly tenable in this modern era to
consider substantial changes in management without adequate, easily
understandable evidence. Accrual to large clinical trials to address
these important issues is in the best interests of breast cancer
patients and can be accomplished very rapidly with appropriate input.
Surgeons in this country will benefit by providing leadership in the
rational management of breast cancer and should consider this an open
invitation to participate in these trials and to urge patients to do
the same.